Celiac disease is a typical malabsorption syndrome, and is associated with higher rates of numerous deficiencies, including folate and vitamin B12. People with celiac disease face higher rates of Hyperhomocysteinemia than do healthy controls.

A team of Dutch researchers led by Dr. Muhammed Hadithi recently set out to evaluate the efficacy of daily supplements of vitamin B6, B12 and folate on homocysteine levels in patients with celiac disease.
The study measured levels of vitamin B6, folate, vitamin B12, and fasting plasma homocysteine in 51 adults with celiac disease and 50 healthy control subjects of similar age and sex.

The results show that the celiac disease subjects who used vitamin supplements had higher blood levels of vitamin B6 (P = 0.003), folate (P < 0.001), and vitamin B12 (P = 0.012) than celiac patients who did not use supplements, or healthy controls (P = 0.035, P < 0.001, P = 0.007, for vitamin B6, folate, and vitamin B12, respectively).

Patients who use vitamin supplements also showed lower levels of plasma homocysteine than in patients who did not (P = 0.001) or healthy controls (P = 0.003). Vitamin B6 and folate were both associated with homocysteine levels, whereas vitamin B12 was not. Twenty-four (48%) of 50 controls and 23 (50%) of 46 of the celiac disease patients carried the MTHFR thermolabile variant T-allele (P = 0.89).

The research team concludes that Homocysteine levels are dependent on Marsh classification and the regular use of B-vitamin supplements reduces of homocysteine levels in patients with celiac disease.The study confirms earlier studies suggesting that both the presence and severity of celiac disease determined homocysteine levels.

The regular use of supplemental B vitamins resulted in higher levels of serum vitamin B6, folate, vitamin B12 and lower levels of plasma homocysteine in patients with celiac disease. Moreover, supplemental B vitamins seem to offer protection against the effects of villous atrophy on homocysteine levels, independent of the genetic susceptibility status as determined by carriage of the C677T polymorphism of 5,10 methylenetetrahydrofolate reductase.

World J Gastroenterol. 2009;15:955–960

According to health officials, about 1% of the population, or one out of every 100 Americans suffers from celiac disease. Currently, that total number of Americans with celiac disease stands somewhere near 3 million. Sadly, upwards of 97% of those affected remain undiagnosed.

For people with celiac disease, eating gluten—a protein found in wheat, rye and barley—causes damage to the lining of the small intestine, preventing the uptake of nutrients.

Delayed diagnosis can put people at risk for certain types of cancer and many other associated conditions, including infertility. Early diagnosis of celiac disease is actually quite easy and carries many advantages.

Still, the average time for a correct diagnosis of celiac disease is 10 years from the first onset of symptoms. That figure is 12 years for Canadians, according to a 2007 survey of the 5000 member Canadian Celiac Association. Checking for celiac disease involves a simple blood test and usually a biopsy to follow up on positive results. Until now, that blood test was available solely through a doctor. Often, believing celiac to be rare, doctors are reluctant to order the blood test without overwhelming evidence. This can be problematical, as most people being diagnosed these days do not have classical symptoms, and are often asymptomatic. Numerous people have been forced to visit multiple doctors before confirming their diagnosis.

Recently, the Finnish firm AniBiotech developed a unique, patient-friendly celiac disease test kit that can be used to provide quick, accurate results at home. Marketed in Canada by 2G Pharma, the Biocard™ Celiac Test Kit works by metering gluten antibody levels from a tiny fingertip blood sample, and is the currently the only point-of-care celiac disease test kit approved by Health Canada.

The test tells users with a high degree of accuracy that they are either negative, developing celiac disease, or already have celiac disease. In the last two cases, the specially formulated Canadian kit encourages people to consult a physician for confirmation, which usually involves a biopsy of the small bowel.

The Biocard™ Celiac Test Kit is currently available in Canada at London Drugs, Rexall Pharma Plus, and other major Canadian retail chains. More information can be found at Open Original Shared Link.

The test kit is currently awaiting approval for U.S. distribution.

It’s been well documented that, for most people celiac disease, a gluten-free diet leads to healing of the small intestine, and brings about overall improvements in their quality of life. Current medical wisdom dictates that once a person is diagnosed with celiac disease and experiences an improvement in symptoms by adopting a gluten-free diet, there is little need to undergo follow-up screening unless they experience a clear recurrence of symptoms.

Some doctors are beginning to challenge that practice. However, it is also becoming clear that people with celiac disease face a higher risk of risk of developing a number of long-term complications and other autoimmune disorders.

The list of such complications and conditions associated with celiac disease is growing rapidly, in particular, autoimmune disease, malignancy, and bone disease. Can these be prevented and outcomes improved? Risk factors that can predict or shape long-term outcomes include genetic make-up, environmental factors, especially gluten consumption and exposure, persistent small intestinal inflammationâ„ damage and nutritional deficiencies.

The use of genotyping has yet to establish a clinical role in the long-term management of duodenal biopsy. Symptoms, blood tests, or other non-invasive methods are poor predictors of healing status, or the likelihood of associated complications. This means that long-term management of celiac care might benefit from strategies laying somewhere between regular biopsies for life and simple faith that one is successfully following a gluten-free diet.

A team of doctors based in Australia recently set out to conduct a systematic review of the complications and associations of celiac disease, to identify potential risk factors, to define ways of assessing risk factors and to provide a strategy for management. The team was made up of Dr. M. L. Haines, Dr. R. P. Anderson & Dr. P. R. Gibson, and they conducted a review of medical literature going back to 1975.

The doctors found that all people with celiac disease should have follow-up exams. They felt a reasonable minimum for all patients would be an initial consultation 1–2 weeks after biopsy diagnosis, review consultation 3–6 months later and subsequent annual reviews assessed on an individual basis.

As to whether the follow-up should be done by a specialist, such as a gastroenterologist, or by a general practitioner, a nurse practitioner, or a dietitian, the research team noted that most celiac patients prefer to see a dietitian for follow-up, with a doctor available as needed.

The team felt that special attention should be paid to patient adherence to a gluten free diet.

The doctors noted the ease of gluten ingestion and pointed out that 6 in 10 patients experience persistent histological changes within an average of two years of undetected gluten exposure. They also noted there are a large number of associated conditions that can be averted by keeping celiac disease under control. They also note that symptoms and blood tests are poor indicators of intestinal damage levels on a cellular level.

Such damage can spread from the cellular level to the systemic level over time, leaving people with untreated celiac disease face an elevated risk of developing infection. The researchers noted that people untreated celiac disease have significantly reduced levels of leucocytes, total lymphocytes, and CD3+, CD4+ and CD8+ lymphocytes compared to those with treated celiac disease and to the general population.

With so many associated conditions tied to celiac-related intestinal damage, controlling or preventing that damage becomes crucial. They also note that proper monitoring of celiac disease can help to prevent celiac-associated neuro-psychiatric conditions such as anxiety, headaches, behavioral symptoms and depression, which, it is thought may be triggered by impaired availability of tryptophan and disturbances in central serotonergic function.

The proper control of celiac disease can help to prevent the development of, or improve, numerous celiac-associated conditions. That proper control means a reliable means to assess patients for follow-up, and the study presents several aspects of a new protocol for treating celiac disease over the course of the patient’s lifetime.

Aliment Pharmacol Ther 28, 1042–1066

Because metabolites are excreted from the cells into blood and urine, collecting these samples can be easy, noninvasive, and inexpensive. Chemical techniques like nuclear magnetic resonance (NMR) spectroscopy are used to analyze the samples. The results of NMR spectroscopy are chemical patterns, showing the simultaneous alterations of many compounds. The measurement and analysis of multiple metabolite changes in response to genetic changes or environmental stimuli is known as metabonomics.

Metabonomics has a number of potential applications. Ease of sample collection may enable researchers to develop a rapid screening tool for diseases like celiac disease. Using metabonomics, it is not necessary to know the specific metabolites that differ in people with a given disease (the disease biomarkers). Rather than looking for the presence or absence of a particular biomarker, the overall pattern of metabolite concentrations is compared to patterns of people known to have the disease (the metabolic signature of the disease) and patterns of people who do not have the disease. Large numbers of metabolites are analyzed simultaneously, instead of one by one, providing a snapshot into what is happening in the cells at a given time.

In this first study to investigate the metabonomic signature of celiac disease, blood and urine samples of 34 people with celiac disease were analyzed at the time of diagnosis, which was based on antibody tests and confirmed with biopsies of the small intestine. These patterns were compared to the metabolite patterns of 34 people without celiac disease. Using blood samples, researchers were able to predict celiac disease up to 83% of the time. Analysis of urine samples gave accuracy of about 70%.

These accuracy rates are lower than those achieved with antibody tests, but this is only the first small study and refining the techniques may significantly improve accuracy rates.In addition, analyzing the metabolic signature may lead to a greater understanding of celiac disease and the cause of its various symptoms. For example, results from this study included lower levels of some metabolites such as pyruvate (a product of glucose breakdown) coupled with elevated levels of other metabolites such as glucose and 3-hydroxybutyric acid (a by-product of fat breakdown) in people with celiac disease.

These results suggest a possible explanation for chronic fatigue experienced by up to 87% of patients with celiac disease—a possible impairment in the body’s ability to use glucose for energy. As expected, evidence of altered gut bacteria was also found, as were an increase in metabolites that indicate an increased intestinal permeability (“leaky gut”). After 12 months of a strict gluten-free diet, these altered metabolite patterns reverted to normal.

Metabonomics is an emerging field of study, which like genomics, holds great promise in the understanding, diagnosis, and treatment of diseases like celiac disease.

Reference:
Bertini I, et al. The metabonomic signature of celiac disease. Journal of Proteome Research. 2008 Dec 11 [Epub ahead of print]

There is currently no cure for the celiac disease. The only treatment is life-long adherence to a strict gluten-free diet. If a gluten-free diet is not followed, the disease can ultimately lead to ill health and life-threatening conditions including malnutrition, osteoporosis, bowel cancer, and may cause infertility problems.

The charity group Coeliac UK, recently hosted a conference at the Royal Society of Arts in central London where, among the latest findings in celiac disease research, they announced progress on the development of a possible vaccine for the condition.

Dr. Bob Anderson of the Autoimmunity and Transplantation Division of Australia’s Walter and Eliza Hall Institute has led a research team that has isolated the toxic elements of gluten, paving the way for a possible vaccine that will suppress or prevent gluten toxicity. The research indicates that the toxic, autoimmune response in celiac patients exposed to wheat is triggered by just few dominant peptides in the gluten protein. This small number of offending peptides makes it exponentially easier for researchers to develop a vaccine.

Dr. Anderson is a joint founder and CEO of Nexpep, an Australian company that is actively working to develop a vaccine to treat celiac disease. Dr. Anderson’s team has created a peptide-based therapeutic vaccine to treat the main problem T-cell epitopes of gluten. The vaccine has the potential to treat at about 80% of people with celiac disease and having the appropriate genetic background. Similar to traditional desensitization therapy for allergies, the peptide-based vaccines are given in multiple small doses over a course of injections in an effort to create immune tolerance not only to the selected gluten fragments, but also lower the toxicity of related toxic gluten molecules.

Nexpep is currently raising capital for a clinical trial program for a peptide-based therapeutic vaccine and intends to commence a Phase 1 clinical trial in the first half of 2009.

Reference:
Open Original Shared Link

It took a major virus, three doctors, x-rays, blood tests toget to Emma’s diagnosis.One doctor toldme “kids throw up” (once every nine days? Really?), a second opinionrecommended Milicon for her “gassy” tummy. Luckily, it all ended the way it should have, with a diagnosis of celiacdisease that only took about 5 months—which is relatively little compared tosome of the stories you’re about to hear.

One woman wrote me describing her daughter’s symptoms whenshe was diagnosed at age 15, but then she wrote back about the subsequentdiagnoses of her sister and mother.Jeanwas diagnosed at age 70 but she and her family tell me her severe scoliosis atage 12 was a symptom! Can you believebeing misdiagnosed for 58 years?Jean evenhad to be put in a back cast for a time.

Jean’s daughter, Vicky was diagnosed with Crohn’s disease atthe age of 12—which included 3 major surgeries! Her celiac disease diagnosis didn’t comeuntil the age of 51. By then major damagehad been done to her body with the onsets of several health issues:rheumatoid and osteo arthritis, thyroiddisease, severe osteoporosis (both hips have been replaced ...one twice)and severe scoliosis. It turns out: three generations of women in the samefamily all started showing their symptoms in those early teen years.

Kim wrote me and said she was diagnosedat 39 years old when she was hospitalized with stomach pain, vomiting anddiarrhea.But she added at the end ofher note, “ probably shouldhave gotten tested at [age] 11 when I had the same severe cramping that put mein the hospital.” The bright spot inthis story is that her eventual celiac diagnosis, led to the quicker diagnosisof her 5-year-old daughter who was just beginning her symptoms of low weightand anemia.

Another contributorsaid her 14-year-old son was diagnosed with celiac two years ago, but has alsohad a kidney issue for the last 9 years.But since he has been eating gluten free…his kidneys have also gottenbetter, last report was the best since before he was brought in at age 5!! Now I wonder which really came first?”It does make you wonder.

But there are somesuccess stories:

One mom mentionedher son’s quick diagnosis. “[it] started with diarrhea. Thought it was a stomach bug.” Then it moved to constipation and two weekslater things still weren’t right.Thentheir doctor put two and two together, “[An]amazing pediatrician said ‘This sounds like Celiac’ and ran the bloodtests. Andrew was only ‘sick’ about 1 month before diagnosis,” shesaid. However looking back on it all, hehad a big belly and slow to grow.

Others talked about having celiac disease and not even feeling sick.

• “I onlyfound out about the anemia through a blood test done as part of a completephysical; my general health to that point was excellent, including runningmarathons,” Danny wrote.
• “The only reason [my 3-year-old daughter]was diagnosed was her yearly blood draw came back positive so we had thebiopsy,” said Monica, a mom of two celiac children.
• Anna’s dad, Tom, was diagnosed in his 40s aftera family-round of blood testing. He isasymptomatic.

The last two pointsshow how important it is to take part in preventative measures, by gettingregular blood testing done for first-degree family members. The National Institute of Diabetes, Digestiveand Kidney Diseases says, “…because celiac disease is hereditary, familymembers of a person with the disease may wish to be tested. Four to 12 percentof an affected person’s first-degree relatives will also have the disease.”Open Original Shared Link

The stories ofdiagnosing celiac disease may leave many of us angry, frustrated, and possiblygrateful—all at the same time. The missed diagnoses and misdiagnoses of those who have thisdisease presents a roller-coasterride of emotions. I hope this articlehelps you in knowing many others have gone through it and are likely goingthrough it as we speak.We just need tomake sure we’re spreading the word and getting as much awareness out there aspossible to help others in similar situations.

A team of researchers recently set out to assess salivary RIA tTG-Abs in celiac children on gluten-free diet. The research team included doctors M. Bonamico, R. Nenna, R.P.L. Luparia, C. Perricone, M. Montuori, F. Lucantoni, A. Castronovo, S. Mura; A. Turchetti, P. Strappini, and C. Tiberti.

The team evaluated blood and saliva samples taken from 109 children at the time of their diagnosis for celiac disease. The first group included 71 females, with an average age of 9.4 years. A second group included 58 people who were following a gluten-free diet. The second group was broken into two subgroups: group 2a with 36 patients assessed at 3-6 months; and group 2b with 34 patients at 9 months or more (group 2b).

The research team also included two control groups matched for age and sex. Group 3 included 89 gastroenterological patients, while group 4 included 49 healthy subjects. The team used RIA to detect tTG-Abs in saliva and blood, and compared the results against two other established tests: serum tTG-Abs ELISA and IgA anti-endomysium antibodies (EMA).

The team detected salivary RIA tTG-Abs in 94.5% of patients from group 1, 66.7% of celiac patients from group 2a, and 50.0% from 2b. They detected blood RIA tTG-Abs in 98.2% of patients from group 1, 72.2% of celiac patients from group 2a, and 50.0% from 2b. The longer patients were on a gluten-free diet, the more the tTG-Abs decreased. The research team also found a correlation between saliva and serum levels (r = 0.75, P = 0.0001). A celiac disease follow-up showed comparable salivary and serum RIA sensitivities, and higher levels for EMA and ELISA methods.

The research team concluded that it is possible to measure salivary tTG-Abs with a high level of accuracy; both at initial diagnosis for celiac disease, and also while patients are following a gluten-free diet.

This discovery means that doctors treating people with celiac disease might soon be able to use a simple saliva test to monitor the progress of their patients’ gluten-free diets. Such a development might take remove much of the guesswork for celiacs who are trying to follow a gluten-free diet, and would be particularly useful for patients who might be asymptomatic, or who are at risk for celiac-associated conditions.

Aliment Pharmacol Ther.  2008; 28(3): 364-370.

A research team recently set out to compare multiplex immunoassay (MIA) testing for antibodies against enzyme-linked immunosorbent assay (ELISA) testing for antibodies in biopsy-proven celiac patients and control subjects, and to determine the helpfulness of using the two tests in combination for making diagnosis of celiac disease.

The research team was made up of doctors S. Rashtak, M. W. Ettore, H. A. Homburger & J. A. Murray. Doctors Rashtak and Murray are with the Mayo Clinic in Rochester, Minnesota.

The team compared sensitivity, specificity and accuracy of MIA and ELISA testing methods for TTG and DGP antibodies in 92 adults with untreated celiac disease, and 124 healthy control subjects. For every test, except TTG IgG, the results showed strong agreement and a significant correlation between the results of MIA and ELISA methods (j > 0.8, r > 0.7). For TTG IgG, both showed low sensitivity (MIA-13.0% vs. ELISA-28.3%), high specificity (MIA-100.0% vs. ELISA-96.8%), and about the same levels of overall accuracy (MIA-63.0% vs. ELISA-67.6%).

They found no significant differences between diagnosis accuracy made using the MIA method compared to diagnosis made using ELISA, or between either of those against a combination of the two methods.

Compared to using either test alone, using both tests together made for a slight increase in overall test sensitivity where any one of the tests was positive, and an increase in specificity when all tests were positive.

The team determined that MIA testing for antibodies is as accurate as ELISA for celiac disease diagnosis and offers practical advantages over ELISA method. MIA testing measures multiple antibodies simultaneously, provides a complete antibody phenotype, and offers a quicker turnaround time and lower cost. They further noted that carefully targeted combination testing can help identify patients who require intestinal biopsy, which may reduce unnecessary biopsies.

Aliment Pharmacol Ther 28, 805–813

In the first study of its kind, a team of researchers based in Ireland set out to analyze enterocyte morphology and cytoskeletal structures using a high content analysis technology.

The research team was made up of doctors Bashir M. Mohamed, Conleth Feighery, Yvonne Williams, Anthony Davies, Dermot Kelleher, Yuri Volkov, Jacinta Kelly and Mohamed Abuzakouk.

The team examined duodenal biopsies from 14 untreated and 10 treated celiac patients and from 20 non-celiac control subjects. They also investigated tissue sections from six study group subjects before and after the development of gluten-sensitive enteropathy.

The research team used an anti-α-tubulin antibody to conduct immunohistochemical studies on paraffin-embedded tissue sections. They found important differences in enterocyte morphology and intracellular cytoskeletal structures in the patients with proven celiac disease and those in the study group.

Moreover, the team observed that these changes existed in the study group prior to any indication of enteropathy, as determined by standard microscopy.

This is the first time researchers have used high content analysis to show specific details of enterocyte morphology. Such an approach permits doctors to quantitatively analyze enterocyte intracellular structure from standard biopsy samples and allows for detection of minute changes that develop before the classic histological lesion.

This process could become important for improving the diagnosis of celiac disease. If doctors can spot celiac-related intestinal lesions before they develop, they can begin to prevent celiac disease before it develops and thereby save lives.

Central European Journal of Biology
Volume 3, Number 3 / September, 2008

In an effort to find out if present current diagnostic criteria are in fact too narrow, Finnish researchers led by Markku Maki, MD, professor of pediatrics at the University of Tampere, Celiac Disease Study Group, Tampere, Finland, evaluated 145 patients who were presumed to have celiac disease. Just under half (71) of the patients showed positive endomysial antibodies, and out of these only 48 patients met the textbook definition for celiac disease.

The research team then split the 23 patients left into two groups. They put the first group on a gluten-free diet for one year, and the second group on a on a standard gluten-inclusive diet for one year. At the end of the year, the doctors conducted follow-up biopsies on all 23 patients. The doctors discovered that the patients who had been on the gluten-free diet did in fact have celiac disease (even though they didn't have any obvious symptoms), and any symptoms that they did have disappeared—they lost their endomysial antibodies and any inflammation that was detected in their intestinal mucosa.

On the other hand, the patients in the second group whose diets included gluten showed no such positive changes, and their symptoms continued. The still showed positive endomysial antibodies, along with inflammation of intestinal mucous membrane, and gluten-induced lesions in the small intestine.

The study director said that each of the patients on the gluten-free diet had chosen to remain gluten-free thereafter, and that the patients on the gluten-inclusive diet had chosen to eliminate gluten from their diets and over time also became symptom-free—endomysial antibody-free and showed signs of healing of the mucous membrane.

Other studies have shown that over time untreated patients who show positive endomysial antibodies may develop the gut injury that is currently required as part of the criteria for diagnosing celiac disease. A greater understanding of the negative effects of untreated or undiagnosed celiac disease, coupled with better testing methods have led to a new strategy that allow doctors to detect celiac disease as early as possible—before any serious damage can occur—this new strategy is likely to be resoundingly welcome among celiac disease sufferers.

 Hopefully the results of this study and others like it will lead to a new awareness among doctors, and will ultimately lead to better methods for diagnosing celiac disease at an earlier stage. This could ultimately mean less suffering and long term physical damage for many people.

Presented at 2009 Digestive Disease Week in San Diego, CA by Dr. Kurppa, a member of Dr. Maki’s research team, on Tuesday, May 20 at 10:30 a.m. Pacific Time in room 10 (San Diego Convention Center).

Shortly after the release of a recent paper by Italian researchers demonstrating that a peptide from durum wheat is able to completely suppress the immune response to gluten in a culture of celiac disease intestinal T cells (see Open Original Shared Link ), I contacted ActoGeniX to suggest they work with the Italian researchers to create an ActoBiotic™ designed to continuously secrete the durum wheat peptide as a therapy for celiac disease. ActoGeniX replied and was very interested in the durum wheat peptide, indicating it was possible for them to produce an ActoBiotic™ to secrete the durum wheat peptide and they would contact the Italian group. I also attempted to contact the Italian researchers to inform them about ActoGeniX, but they did not reply. I strongly believe that a collaboration between these two groups would result in the speediest and most successful development of a treatment which could effectively "cure" celiac disease through continuous secretion of the durum wheat peptide by genetically modified probiotic bacteria in the gut.

ActoGeniX has recently totally revised their website which is now much more informative and includes short videos discussing ActoBiotics™ as well as a short video presentation of their celiac disease research. More about this article can be found on their website at Open Original Shared Link.

Technical information describing their product and initial research and development in detail is presented in the following patent application:  Open Original Shared Link.

A team of researchers led by Dr. Grzegorz Telega recently surveyed medical records of people diagnosed with celiac disease at Children's Hospital of Wisconsin from 1986 to 2003. The statistics showed that the number of celiac disease diagnosis rose from a single case in 1986 to 93 cases in 2003. The total number of cases during that period was 143.

Before the mid-1990’s, more than 85% of children diagnosed with celiac disease were under 10 years old, with the average age being just over 5 years old. After 1995, less than 50% of children diagnosed with celiac disease were under 10 years old, and the average age at diagnosis had risen to about 8.5 years of age. Children diagnosed before the age of 3 years old usually complained of classic celiac-associated gastrointestinal symptoms, such as malnutrition, diarrhea, abdominal pain, and bloating, while children diagnosed at older ages had less pronounced symptoms.

One of the important conclusions made by the research group is that the possibility of celiac disease should be strongly considered in people with other autoimmune disorders, even if those people do not show gastrointestinal symptoms traditionally associated with celiac disease.

The research team called upon primary care doctors to adopt a practice of celiac screening for all people with elevated risk factors, including people with a family history of celiac disease, people with Addison’s disease Down Syndrome type 1 diabetes, thyroiditis, Turner syndrome, and type 1 diabetes. The team also called for screening of patients with short stature, iron deficiency anemia, and high transaminase levels.

Arch Pediatr Adolesc Med 2008;162:164-168.